2-Aminothiophene-3-carboxylic acid esters and their 3-carbonitrile analogues are commonly used for the synthesis of 2-unsubstituted thieno[2,3-d]pyrimidines. These compounds were endowed with biological activity). A variety of 2-aminothiophene-3-carboxylates and carboxamides, in particular 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene and 2-amino-5,6,7,8-tetrahydrocyclohepta[b]thiophenes with 3-carboxylate and 3-carboxamide substituents were found to behave as adenosine A1 receptor allosteric enhancers and 2-amino-4,5,6,7-tetrahydro N-phenylbenzo[b]thiophene-3-carboxamides were endowed with anti-arrhythmic, serotonin antagonist and anti-anxiety activities. Several 2-aminothiophene analogues were also shown to exhibit anti-inflammatory potential. All above-mentioned compound classes were synthesized starting from 2-aminothiophene-3-carboxylic acids which resulted in the formation of thiophenes containing a fixed ring system. Interestingly, the fluorophenyl derivative of the thiophene 2-ureido-3-carboxylic acid amide TPCA-1 has recently been identified as a small molecule IKB kinase β (IKKβ) inhibitor.
Recently, we have synthesized a series of 2-amino-3-aroyl-4-substituted thiophene derivatives as anti-proliferative agents. They seem to inhibit tubulin polymerization, resulting in an accumulation of a proportion of the drug-exposed cells in the G2/M and sub-G1 phases of the cell cycle (Romagnoli et al., 2010) (1). However the compounds discovered in Romagnoli et al., 2010 showed no selectivity. Thus there is still a big need for very active and selective anti-proliferative compounds in this field and such selective and active compounds are useful for treating hyperproliferative disorders.